The apparent increase in adrenergic activity observed in the organism in the hyperthyroid state in the presence of a normal level of circulating catecholamines may result from enhanced responsiveness to basal or threshold concentrations of catecholamines. This may result from an increase in the number of B-receptors demonstrated recently. The purpose of the present study was to measure the cAMP-dependent protein kinase activation and contractile response subsequent to threshold levels of B-stimulation with isoproterenol in the hyperthyroid and euthyroid heart. These studies were also performed at maximal doses of isoproterenol. In addition, since the protein kinase mediated phosphorylation of sarcoplasmic reticulum and subsequent enhancement of Ca ions transport appears to be integral to the contractile response, we also measured stimulation by cAMP-dependent kinase of Ca ions accumulation in sarcoplasmic reticulum enriched microsomal preparations from euthyroid and hyperthyroid hearts.